Abuse-deterrent pharmaceutical compositions of opioids and other drugs

Abstract

An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. In a preferred embodiment, a drug is modified to increase its lipophilicity. In some embodiments the modified drug is homogeneously dispersed within spherical microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and/or organic solvent insoluble. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract.

We claim: 
     
       1. An abuse-deterrent oral dosage form comprising a plurality of microparticles, wherein each microparticle comprises a homogenous single phase comprising:
 (a) oxycodone; and 
 (b) one or more fatty acids; 
 wherein the molar ratio of fatty acid to oxycodone is in excess of about 7:1 and the oxycodone is in the form of a fatty acid salt. 
 
     
     
       2. The abuse-deterrent oral dosage form of  claim 1 , wherein the one or more fatty acids is linoleic acid, octanoic acid, lauric acid, stearic acid, palmitic acid, myristic acid, or oleic acid. 
     
     
       3. The abuse-deterrent oral dosage form of  claim 2 , wherein the one or more fatty acids is stearic acid, palmitic acid, or myristic acid. 
     
     
       4. The abuse-deterrent oral dosage form of  claim 3 , wherein the fatty acid is myristic acid. 
     
     
       5. The abuse-deterrent oral dosage form of  claim 1 , wherein the microparticles further comprise one or more carrier materials. 
     
     
       6. The abuse-deterrent oral dosage form of  claim 5 , wherein the one or more carrier materials comprise fats, fatty substances, waxes, wax-like substances or mixtures thereof. 
     
     
       7. The abuse-deterrent oral dosage form of  claim 6 , wherein the one or more carrier materials comprise beeswax, carnauba wax, hydrogenated oil or mixtures thereof. 
     
     
       8. The abuse-deterrent oral dosage form of  claim 7 , wherein the one or more carrier materials comprise beeswax, carnauba wax, or mixtures thereof. 
     
     
       9. The abuse-deterrent oral dosage form of  claim 8 , wherein the fatty acid is myristic acid. 
     
     
       10. The abuse-deterrent oral dosage form of  claim 1 , wherein the oral dosage form is a capsule or a tablet. 
     
     
       11. The abuse-deterrent oral dosage form of  claim 10 , wherein the oral dosage form is a capsule. 
     
     
       12. The abuse-deterrent oral dosage form of  claim 1 , wherein the oral dosage form further comprises an antioxidant. 
     
     
       13. The abuse-deterrent oral dosage form of  claim 12 , wherein the antioxidant comprises butylated hydroxy toluene (BHT); ascorbic acid, its salts and esters; Vitamin E, tocopherol and its salts; sodium metabisulphite; cysteine; citric acid; propyl gallate; butylated hydroxyanisole (BHA); or combinations thereof. 
     
     
       14. The abuse-deterrent oral dosage form of  claim 1 , wherein each microparticle further comprises an enteric coat. 
     
     
       15. The abuse-deterrent oral dosage form of  claim 1 , wherein the oral dosage form is a controlled-release oral dosage form. 
     
     
       16. The abuse-deterrent oral dosage form of  claim 1 , wherein each microparticle further comprises a pharmaceutically acceptable surfactant. 
     
     
       17. The abuse-deterrent oral dosage form of  claim 1 , wherein the microparticles are spherical. 
     
     
       18. The abuse-deterrent oral dosage form of  claim 1 , wherein the oral dosage form retards the release of the one or more drugs prone to abuse, even if the physical integrity of the dosage form is compromised and the compromised dosage form is placed in water. 
     
     
       19. A method of making the abuse-deterrent oral dosage form of  claim 1 , wherein the oxycodone, in the form of a free base, is dissolved in a hot melt solution comprising the one or more fatty acids and wherein the molar ratio of fatty acid to oxycodone is in excess of about 7:1. 
     
     
       20. The method of  claim 19  wherein the one or more fatty acids is linoleic acid, octanoic acid, lauric acid, stearic acid, palmitic acid, myristic acid, or oleic acid. 
     
     
       21. The method of  claim 20 , wherein the one or more fatty acids is stearic acid, palmitic acid, or myristic acid. 
     
     
       22. The method of  claim 21 , wherein the fatty acid is myristic acid.